Noncovalent Interaction Analysis in Fluctuating Environments

Noncovalent interactions play a central role in many chemical and biological systems. In a previous study, Johnson et al. developed a noncovalent interaction (NCI) index to characterize and visualize different types of weak interactions. To apply the NCI analysis to fluctuating environments as in the solution phase, we here developed a new averaged noncovalent interaction (i.e., aNCI) index along with a fluctuation index to characterize the magnitude of interactions and fluctuations. We applied aNCI for various systems including solute-solvent and ligand-protein noncovalent interactions. For water and benzene molecules in aqueous solution, solvation structures and the specific hydrogen bond patterns were visualized clearly. For the Cl- + CH3Cl S(N)2 reaction in aqueous solution, charge reorganization influences over solvation structure along S(N)2 reaction were revealed. For ligand-protein systems, aNCI can recover several key fluctuating hydrogen bond patterns that have potential applications for drug design. Therefore, aNCI, as a complementary approach to the original NCI method, can extract and visualize noncovalent interactions from thermal noise in fluctuating environments.